Patients with stable coronary artery disease may experience episodes of myocardial ischemia during daily life. Circadian and short-term variation in the frequency of these episodes has been demonstrated previously. However, the occurrence of variation over long-time intervals and its relation to variations in ischemic threshold assessed from exercise testing are unknown. We studied 40 patients with ambulatory ECG monitoring and exercise treadmill test at initial evaluation and after a mean follow-up of one year during which no acute events or changes in symptoms occurred. During follow-up, 21 patients (52%) showed a significant change in the magnitude of myocardial ischemia during late in life. Patients who had an increase in the number of ischemic episodes during monitoring showed a significant fall in ischemic threshold (time of exercise at 1 mm of ST segment depression during exercise). Conversely, patients with a reduction in the number of episodes during follow-up had a significantly higher ischemic threshold at their last evaluation. Patients with no change in the number of episodes, also showed no significant changes in the results of exercise testing. These findings indicate that patients with coronary artery disease may experience significant variations in the magnitude of myocardial ischemia in daily life over relatively long periods of time, even without suffering an acute event or changes in symptoms. These changes in ambulatory myocardial ischemia are linked to parallel variations in ischemic threshold, and therefore can be predicted by analysis of the exercise test.